PROJECT SUMMARY Since its inception 40 years ago, in vitro fertilization (IVF) has resulted in the birth of more than 1 million babies in the United States, and has revolutionized the field of reproductive medicine. Unfortunately, the success rate of IVF is still exceedingly low, especially for women >40 years old, with only 15.5% of implanted embryos resulting in pregnancy. This is partly due to the cytological method used for pre-implantation screening, which cannot detect the most common genetic defect during IVF, aneuploidy (i.e. chromosomal copy-number variation). Aneuploidy is linked to higher rates of miscarriage, and occurs more often in women >40 years of age; thus, aneuploidy has been a frequent target for genetic screening to improve IVF outcomes. Pre-implantation genetic testing for aneuploidy (PGT-A) refers to a variety of techniques aimed at detecting changes in chromosomal copy number, with the goal of identifying high-quality euploid embryos for implantation. Recent advances in next-generation sequencing (NGS) technologies have made it possible to screen embryos at higher levels of precision, and across a wider range of genetic defects, including mosaicism, triploidy and single nucleotide polymorphisms (SNPs). Despite these remarkable advances, there are still significant challenges with PGT-A sequencing. Indeed, the most commonly implemented software for PGT-A (i.e. BlueFuse ) are bundled with specific sequencing platforms (i.e. VeriSeq), and are only designed to test for aneuploidy. Furthermore, existing pipelines are not user-friendly or customizable, which is a serious obstacle prohibiting the use of NGS by clinicians / embryologists. A more accessible bioinformatics platform is desperately needed that will bridge the gap between PGT-A sequencing and IVF outcomes. Basepair? is an innovator in efficient, user-friendly, web-based NGS analysis systems, with fully automated ChIP-, RNA-, ATAC-, and DNA-Seq bioinformatics pipelines available online. Here, Basepair will deliver PiNDA?, the first fully integrated software solution for comprehensive PGT-A analysis. In Aim 1, we will develop modules to test for specific chromosomal abnormalities, including mosaicism and triploidy, and validate each model with training data derived from somatic cell lines with known chromosomal aberrations. In Aim 2, we will integrate our modules into the PiNDA software system, creating a user-friendly, web-based interface that will perform full data analysis (raw data to full summary report) in <15 minutes, with no manual input required. Final data will be accessible via Basepair?s online portal, facilitating rapid data transfer from embryologists to physicians, and supporting the integration of NGS tests in IVF. Our innovative bioinformatics platform will accelerate NGS analysis for IVF, improving rates of pregnancy and advancing research in the success of IVF procedures.